The use of body mass index (BMI) may not be the most appropriate measurement tool
in determining obesity in diverse populations. We studied a convenience sample
of 108 African American (AA) women to determine the best method for measuring
obesity in this at-risk population. The purpose of this study was to determine
if percent body fat (PBF) and percent body water (PBW) could be used as
alternatives to BMI in predicting obesity and risk for hypertension (HTN) among
After accounting for age, BMI, and the use of anti-hypertensive medication, PBF
(p = 0.0125) and PBW (p = 0.0297) were significantly associated with systolic
blood pressure, while BMI was not. Likewise, PBF (p = 0.0316) was significantly
associated with diastolic blood pressure, while PBW and BMI were not. Thus,
health care practitioners should consider alternative anthropometric
measurements such as PBF when assessing obesity in AA women.
obesity; African American; women; percent body fat; body mass index
The Line Islands are calcium carbonate coral reef platforms located in iron-poor regions of the central Pacific. Natural terrestrial run-off of iron is non-existent and aerial deposition is extremely low. However, a number of ship groundings have occurred on these atolls. The reefs surrounding the shipwreck debris are characterized by high benthic cover of turf algae, macroalgae, cyanobacterial mats and corallimorphs, as well as particulate-laden, cloudy water. These sites also have very low coral and crustose coralline algal cover and are call black reefs because of the dark-colored benthic community and reduced clarity of the overlying water column. Here we use a combination of benthic surveys, chemistry, metagenomics and microcosms to investigate if and how shipwrecks initiate and maintain black reefs. Comparative surveys show that the live coral cover was reduced from 40 to 60% to <10% on black reefs on Millennium, Tabuaeran and Kingman. These three sites are relatively large (>0.75 km2). The phase shift occurs rapidly; the Kingman black reef formed within 3 years of the ship grounding. Iron concentrations in algae tissue from the Millennium black reef site were six times higher than in algae collected from reference sites. Metagenomic sequencing of the Millennium Atoll black reef-associated microbial community was enriched in iron-associated virulence genes and known pathogens. Microcosm experiments showed that corals were killed by black reef rubble through microbial activity. Together these results demonstrate that shipwrecks and their associated iron pose significant threats to coral reefs in iron-limited regions.
coral reef; iron; metagenomics; microbes; phase shift; shipwreck
TC83 is a human vaccine with investigational new drug status and is used as a prototype Venezuelan equine encephalitis virus for pathogenesis and antiviral research. Differing from other experimental models, the virus causes high titer infection in the brain and 90–100% mortality in the C3H/HeN murine model. To better characterize the susceptibility to disease development in C3H/HeN mice, we have analyzed the gene transcriptomes and cytokine production in the brains of infected mice. Our analysis indicated the potential importance of natural killer cells in the encephalitic disease development. This paper describes for the first time a pathogenic role for natural killer cells in VEEV encephalitis.
Alphavirus; Immunology; Natural killer cells; Encephalitis; VEEV
Vaccines against emerging pathogens such as the 2009 H1N1 pandemic virus can benefit from current technologies such as rapid genomic sequencing to construct the most biologically relevant vaccine. A novel platform (Ad5 [E1-, E2b-]) has been utilized to induce immune responses to various antigenic targets. We employed this vector platform to express hemagglutinin (HA) and neuraminidase (NA) genes from 2009 H1N1 pandemic viruses. Inserts were consensuses sequences designed from viral isolate sequences and the vaccine was rapidly constructed and produced. Vaccination induced H1N1 immune responses in mice, which afforded protection from lethal virus challenge. In ferrets, vaccination protected from disease development and significantly reduced viral titers in nasal washes. H1N1 cell mediated immunity as well as antibody induction correlated with the prevention of disease symptoms and reduction of virus replication. The Ad5 [E1-, E2b-] should be evaluated for the rapid development of effective vaccines against infectious diseases.
Viral shedding; Influenza; H1N1 vaccine; Adenovirus vector; Ad5 [E1-, E2b-]; Hemagglutinin; Neuraminidase; Cell mediated immunity; Pandemic; Horizontal transmission
Transmission of highly pathogenic avian influenza (HPAI) between birds and humans is an ongoing threat that holds potential for the emergence of a pandemic influenza strain. A major barrier to an effective vaccine against avian influenza has been the generally poor immunopotency of many of the HPAI strains coupled with the manufacturing constraints employing conventional methodologies. Fusion of flagellin, a toll-like receptor-5 ligand, to vaccine antigens has been shown to enhance the immune response to the fused antigen in preclinical studies. Here, we have evaluated the immunogenicity and efficacy of a panel of flagellin-based hemagglutinin (HA) globular head fusion vaccines in inbred mice. The HA globular head of these vaccines is derived from the A/Vietnam/1203/04 (VN04; H5N1) HA molecule. We find that replacement of domain D3 of flagellin with the VN04 HA globular head creates a highly effective vaccine that elicits protective HAI titers which protect mice against disease and death in a lethal challenge model.
Avian flu vaccine; HA globular head; Prokaryotic production
Global data on human papillomavirus serological and DNA prevalence are essential to optimize HPV prophylactic vaccination strategies.
We conducted a global review of age-specific HPV antibody and studies with both antibody and DNA prevalence for HPV types 16, 18, 6 and 11.
One hundred-seventeen studies were included; participants’ ages ranged from several hours to over 90 years. HPV 16 seroprevalence was generally higher in Africa, Central and South America, and North America, more prevalent among women than men, and peaked around ages 25-40 years. HPV 18 seroprevalence was generally lower than HPV 16 with a later age peak. Data were limited for HPV 6 and 11, which both peaked at ages similar to HPV 18. In 9-26 year-old females, HPV 16 seroprevalence ranged from 0-31% in North America, 21-30% in Africa, 0-23% in Asia/Australia, 0-33% in Europe, and 13-43% in Central and South America. HPV 16/18 DNA prevalence peaked 10-15 years before corresponding HPV 16/18 antibody prevalence.
Females within the HPV-vaccine eligible age group (9-26 years) had a range of dual HPV 16 DNA and serology negativity from 81-87%, whereas 90-98% were HPV 16 DNA negative. Serology and DNA data are lacking worldwide for females younger than age 15 years, the prime target group for vaccination.
Global; Human papillomavirus; Serology; DNA; prevalence; immunology; antibodies
Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008–2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2–2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7–48.6) and ICC (OR = 29.5, 95% CI 6.3–38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression.
We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress.
HIV-infected women are at increased risk for developing cervical cancer. Women living in resource-limited countries are especially at risk due to poor access to cervical cancer screening and treatment. We evaluated three cervical cancer screening methods to detect cervical intraepithelial neoplasia grade 2 and above (CIN 2+) in HIV-infected women in South Africa; Pap smear, visual inspection with 5% acetic acid (VIA) and human papillomavirus detection (HPV).
HIV-infected women aged 18–65 were recruited in Johannesburg. A cross-sectional study evaluating three screening methods for the detection of the histologically-defined gold standard CIN-2 + was performed. Women were screened for cervical abnormalities with the Digene HC2 assay (HPV), Pap smear and VIA. VIA was performed by clinic nurses, digital photographs taken and then later reviewed by specialist physicians. The sensitivity, specificity and predictive valves for CIN-2 + were calculated using maximum likelihood estimators.
1,202 HIV-infected women participated, with a median age of 38 years and CD4 counts of 394 cells/mm3. One third of women had a high grade lesion on cytology. VIA and HPV were positive in 45% and 61% of women respectively. Estimated sensitivity/specificity for HPV, Pap smear and VIA for CIN 2+ was 92%/51.4%, 75.8%/83.4% and 65.4/68.5% (nurse reading), respectively. Sensitivities were similar, and specificities appeared significantly lower for the HPV test, cytology and VIA among women with CD4 counts ≤200 cells/mm3 as compared to CD4 counts >350 cells/mm3.
Although HPV was the most sensitive screening method for detecting CIN 2+, it was less specific than conventional cytology and VIA with digital imaging review. Screening programs may need to be individualized in context of the resources and capacity in each area.
The use of Negative Pressure Wound Therapy (NPWT) for temporary abdominal closure of open abdomen (OA) wounds is widely accepted. Published outcomes vary according to the specific nature and the aetiology that resulted in an OA. The aim of this study was to evaluate the effectiveness of a new NPWT system specifically used OA resulting from abdominal trauma.
A prospective study on trauma patients requiring temporary abdominal closure (TAC) with grade 1or 2 OA was carried out. All patients were treated with NPWT (RENASYS AB Smith & Nephew) to achieve TAC. The primary outcome measure was time taken to achieve fascial closure and secondary outcomes were complications and mortality.
A total of 20 patients were included. Thirteen patients (65%) achieved fascial closure following a median treatment period of 3 days. Four patients (20%) died of causes unrelated to NPWT. Complications included fistula formation in one patient (5%) with spontaneous resolution during NPWT), bowel necrosis in a single patient (5%) and three cases of infection (15%). No fistulae were present at the end of NPWT.
This new NPWT kit is safe and effective and results in a high rate of fascial closure and low complication rates in the severely injured trauma patient.
Negative Pressure Wound Therapy (NPWT); Grade 1 and 2 open abdomen; Abdominal trauma; Fascial closure
Background. There is little information on multiple human papillomavirus (HPV) infections and the potential for type competition in men, yet competition may impact the type-specific efficacy of HPV vaccination.
Methods. Among 2702 uncircumcised men in Kisumu, Kenya, who were seronegative for human immunodeficiency virus, the observed numbers of HPV types detected were compared with the expected number, which was simulated under the assumption of independent infections. To assess the potential for HPV type competition, adjusted odds ratios for pairwise combinations of prevalent HPV type infections were estimated using semi-Bayesian methods.
Results. Half of all men were HPV positive, of whom 57% had multiple HPV types. We observed men without HPV infection and with ≥4 HPV types more often than expected if infections were independent. No negative associations between individual HPV types were observed. HPV types 31, 39, 56, 58, and 59 were positively associated with both carcinogenic vaccine types HPV-16 and HPV-18 (2-sided P value <.05).
Conclusions. Men who were HPV infected were likely to test positive for >1 HPV type. Cross-sectional associations between individual HPV types were positive and did not appear to be type-specific. Thus, we did not identify HPV types that are candidates for potential HPV type competition in men.
Alzheimer’s disease (AD) is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD) and non-transgenic (Non-Tg) control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4–10 months), 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ) plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD.
Rapid and accurate identification of disease progression are key factors in testing novel vaccines and antivirals against encephalitic alphaviruses. Typical efficacy studies utilize a large number of animals and severe morbidity or mortality as an endpoint. New technologies provide a means to reduce and refine the animal use as proposed in Hume’s 3Rs (replacement, reduction, refinement) described by Russel and Burch. In vivo imaging systems (IVIS) and bioluminescent enzyme technologies accomplish the reduction of animal requirements while shortening the experimental time and improving the accuracy in localizing active virus replication. In the case of murine models of viral encephalitis in which central nervous system (CNS) viral invasion occurs rapidly but the disease development is relatively slow, we visualized the initial brain infection and enhance the data collection process required for efficacy studies on antivirals or vaccines that are aimed at preventing brain infection. Accordingly, we infected mice through intranasal inoculation with the genetically modified pathogen, Venezuelan equine encephalitis, which expresses a luciferase gene. In this study, we were able to identify the invasion of the CNS at least 3 days before any clinical signs of disease, allowing for reduction of animal morbidity providing a humane means of disease and vaccine research while obtaining scientific data accurately and more rapidly. Based on our data from the imaging model, we confirmed the usefulness of this technology in preclinical research by demonstrating the efficacy of Ampligen, a TLR-3 agonist, in preventing CNS invasion.
IVIS; Luciferase; in vivo; VEEV; TC83; neuroinvasion; encephalitis
Cervical squamous intra-epithelial lesions (SIL) are more frequent in HIV-positive women overall. However the appropriate age at which to begin and end cervical cancer screening for early detection of lesions in HIV-positive women is not clear. We assessed the age-specific prevalence of any SIL and SIL requiring colposcopy in HIV-positive women in Cameroon.
We enrolled, interviewed and conducted conventional cervical cytology in 282 women, aged 19–68 years, initiating antiretroviral therapy in three clinics in Cameroon. In bivariable analyses, the crude relationship between age and the presence of lesions was assessed using locally weighted regression (LOWESS) methods. In multivariate analyses, generalized linear models with prevalence as the outcome, an identity link and a binomial distribution, were used to estimate prevalence differences. Bias analyses were conducted to assess the potential effect of inaccuracies in cytology.
SIL were detected in 43.5% of the 276 women with satisfactory samples, 17.8% of whom had ASC-H/HSIL. On average, women aged 26 to 59 tended to have a slightly higher prevalence of any SIL than other women (Prevalence difference PD: 6.5%; 95%CI: -11.4, 24.4%). This PD was a function of CD4 count (heterogeneity test p-value =0.09): amongst patients with CD4 counts less than 200cells/uL, the prevalence was higher in patients aged 26–59, while there was essentially no difference amongst women with CD4 counts greater than 200 cells/uL. ASC-H/HSIL were present in women as young as 19 and as old as 62. Overall the prevalence of ASC-H/HSIL increased by 0.7% (95%CI: -3.8%, 5.1%) per decade increase in age.
Both severe and less severe lesions were prevalent at all ages suggesting little utility of age-targeted screening among HIV-positive women. Nevertheless, the long-term evolution of these lesions needs to be assessed in prospective studies.
Scorpion venoms have been studied for over fifty years; however, the majority of research has focussed primarily on medically important Buthidae species. Additionally, venoms of the estimated 200 species of scorpion native to Australia have received very little attention. The first venom mass profiles of six non-buthid and one buthid scorpion species are presented herein, four of which are endemic to Australia. While masses under 5 kDa dominated the venoms of all species, the buthid venom contained considerably more masses between 7 and 8 kDa than those of the non-buthids, corroborating the emergent trend that buthids are richer in long-chain neurotoxins than non-buthids. The Australian scorpion venom fractions were also analysed with the relatively new MALDI-ToF matrix 1,5-DAN. Over forty partial sequences were obtained, the majority of which are homologous to scorpion antimicrobials such as opistoporin and IsCT2. Overall, this study is the single most comprehensive mass spectrometric analysis of scorpion venom landscapes to date and provides an insight into untapped Australian species.
scorpion venom; mass landscapes; mass spectrometry
Co-morbid symptoms (for example, chronic pain, depression, anxiety, and fatigue) are particularly common in military fighters returning from the current conflicts, who have experienced physical and/or psychological trauma. These overlapping conditions cut across the boundaries of mind, brain and body, resulting in a common symptomatic and functional spectrum of physical, cognitive, psychological and behavioral effects referred to as the ‘Trauma Spectrum Response’ (TSR). While acupuncture has been shown to treat some of these components effectively, the current literature is often difficult to interpret, inconsistent or of variable quality. Thus, to gauge comprehensively the effectiveness of acupuncture across TSR components, a systematic review of reviews was conducted using the Samueli Institute’s Rapid Evidence Assessment of the Literature (REAL©) methodology.
PubMed/MEDLINE, the Cochrane Database of Systematic Reviews, EMBASE, CINAHL, and PsycInfo were searched from inception to September 2011 for systematic reviews/meta-analyses. Quality assessment was rigorously performed using the Scottish Intercollegiate Guidelines Network (SIGN 50) checklist and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Adherence to the Standards for Reporting Interventions in Clinical Trials in Acupuncture (STRICTA) criteria was also assessed.
Of the 1,480 citations identified by our searches, 52 systematic reviews/meta-analyses, all high quality except for one, met inclusion criteria for each TSR component except post-traumatic stress disorder (PTSD) and sexual function. The majority of reviews addressed most STRICTA components, but did not describe safety.
Based on the results of our review, acupuncture appears to be effective for treating headaches and, although more research is needed, seems to be a promising treatment option for anxiety, sleep disturbances, depression and chronic pain. It does not, however, demonstrate any substantial treatment benefit for substance abuse. Because there were no reviews on PTSD or sexual function that met our pre-defined inclusion criteria, we cannot comment on acupuncture’s effectiveness in treating these conditions. More quality data are also needed to determine whether acupuncture is appropriate for treating fatigue or cognitive difficulties. Further, while acupuncture has been shown to be generally safe, safety was not described in the majority of studies, making it difficult to provide any strong recommendations. Future research should address safety reporting in detail in order to increase our confidence in acupuncture’s efficacy across the identified TSR components.
Acupuncture; Trauma Spectrum Response; Systematic review of reviews; Rapid evidence assessment of the literature (REAL©)
Infantile botulism is a rare cause of neuromuscular weakness resulting from ingestion of Clostridium botulinum—an anaerobic Gram-positive bacillus found universally in soil. The only definite food source known to cause infantile botulism is honey; previously, links to formula milk have been postulated but not definitely sourced. We present an interesting case report of a 2-month-old infant with this rare condition, including the diagnostic difficulties that ensued. A brief overview of the condition follows. This is the first case in the UK in which C botulinum was successfully isolated from both the patient and the suspected source—a jar of honey. The importance of food labelling as a public health message is highlighted.
This case report describes twins presenting approximately 24 h apart both with enterovirus meningoencephalitis. The presenting symptoms are described along with laboratory results. Both had extremely high white cell counts in cerebrospinal fluid, which were predominantly lymphocytes. Clinical course and outcomes are described. There was a potential delay in diagnosis of the second twin given the pathology of the twin sibling and the symptoms presented.
Lassa virus (LASV) is the causative agent of Lassa hemorrhagic fever (LF) in humans, a deadly disease endemic to West Africa that results in 5,000 to 10,000 deaths annually. Here we present results demonstrating that functional type I and type II interferon (IFN) signaling is required for efficient control of LASV dissemination and clearance.
We characterized parental attitudes regarding school HPV vaccination requirements for adolescent girls. Study participants were 866 parents of 10–18 y-old girls in areas of North Carolina with elevated cervical cancer incidence. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression. Approximately half (47%) of parents agreed that laws requiring HPV immunization for school attendance “are a good idea” when opt-out provisions were not mentioned. Far more agreed that “these laws are okay only if parents can opt out if they want to” (84%). Predictors of supporting requirements included believing HPV vaccine is highly effective against cervical cancer (OR = 2.5, 95% CI:1.7–5.0) or is more beneficial if provided at an earlier age (OR = 16.1, 95% CI:8.4–31.0). Parents were less likely to agree with vaccine requirements being a good idea if they expressed concerns related to HPV vaccine safety (OR = 0.3, 95% CI:0.1–0.5), its recent introduction (OR = 0.3, 95% CI:0.2–0.6). Parental acceptance of school requirements appears to depend on perceived HPV vaccine safety and efficacy, understanding of the optimal age for vaccine administration, and inclusion of opt-out provisions.
Public policy; human papillomavirus; cervical cancer; vaccine; mandates; requirements; implementation
Community structure and assembly are determined in part by environmental heterogeneity. While reef-building corals respond negatively to warming (i.e. bleaching events) and ocean acidification (OA), the extent of present-day natural variability in pH on shallow reefs and ecological consequences for benthic assemblages is unknown. We documented high resolution temporal patterns in temperature and pH from three reefs in the central Pacific and examined how these data relate to community development and net accretion rates of early successional benthic organisms. These reefs experienced substantial diel fluctuations in temperature (0.78°C) and pH (>0.2) similar to the magnitude of ‘warming’ and ‘acidification’ expected over the next century. Where daily pH within the benthic boundary layer failed to exceed pelagic climatological seasonal lows, net accretion was slower and fleshy, non-calcifying benthic organisms dominated space. Thus, key aspects of coral reef ecosystem structure and function are presently related to natural diurnal variability in pH.
Our study aimed to assess adult women’s knowledge of human papillomavirus (HPV) and cervical cancer, and characterize their attitudes towards potential screening and prevention strategies.
Women were participants of an HIV-discordant couples cohort in Nairobi, Kenya. An interviewer-administered questionnaire was used to obtain information on sociodemographic status, and sexual and medical history at baseline and on knowledge and attitudes towards Pap smears, self-sampling, and HPV vaccination at study exit.
Only 14% of the 409 women (67% HIV-positive; median age 29 years) had ever had a Pap smear prior to study enrollment and very few women had ever heard of HPV (18%). Although most women knew that Pap smears detect cervical cancer (69%), very few knew that routine Pap screening is the main way to prevent ICC (18%). Most women reported a high level of cultural acceptability for Pap smear screening and a low level of physical discomfort during Pap smear collection. In addition, over 80% of women reported that they would feel comfortable using a self-sampling device (82%) and would prefer at-home sample collection (84%). Nearly all women (94%) reported willingness to be vaccinated to prevent cervical cancer if offered at no or low cost.
These findings highlight the need to educate women on routine use of Pap smears in the prevention of cervical cancer and demonstrate that vaccination and self-sampling would be acceptable modalities for cervical cancer prevention and screening.
Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations.
Association results for a dichotomized cigarettes smoked per day (CPD) phenotype in 27 datasets (European ancestry (N=14,786), Asian (N=6,889), and African American (N=10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations.
We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (p < 0.01) in each of these three populations (OR=1.33, 95%C.I.=1.25–1.42, p=1.1×10−17 in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans.
The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments.
smoking; genetics; meta-analysis; cross-population
We know little about men’s beliefs about human papillomavirus (HPV) vaccine and willingness to receive it. In January 2009, the authors recruited 296 heterosexual men and 312 gay and bisexual men from a national panel of U.S. households to complete an online survey about HPV and HPV vaccine. The authors analyzed data using logistic regression, controlling for age, education, number of lifetime sexual partners, and urban residence. More gay and bisexual men than heterosexual men were willing to receive HPV vaccine (73% vs. 37%; adjusted odds ratio = 4.99; 95% confidence interval = 3.36, 7.49). Gay and bisexual men reported greater awareness of HPV vaccine, perceived worry about HPV-related diseases, perceived effectiveness of HPV vaccine, and anticipated regret if they declined vaccination and later developed HPV-related disease compared with heterosexual men (all ps < .05). The lower acceptability and different beliefs among heterosexual men suggest that novel interventions for this group may be needed.
HPV vaccine; Gardasil; males; gay
Human papillomavirus (HPV) seroprevalence data have not previously been reported for different geographical regions of China. This study investigated the cross-sectional seroprevalence of antibodies to HPV 6, 11, 16, and 18 virus-like particles in Chinese women.
Population-based samples of women were enrolled from 2006 to 2007 in 3 rural and 2 urban areas of China. Each consenting woman completed a questionnaire and provided a blood sample. Serum antibodies were detected using a competitive Luminex immunoassay that measures antibodies to type-specific, neutralizing epitopes on the virus-like particles.
A total of 4,731 women (median age 35, age range 14-54) were included, of which 4,211 were sexually active women (median age 37) and 520 virgins (median age 18). Low risk HPV 6 was the most common serotype detected (7.3%), followed by HPV 16 (5.6%), HPV 11 (2.9%), and HPV 18 (1.9%). Overall HPV seroprevalence to any type was significantly higher among sexually active women (15.8%) than virgins (2.5%) (P = 0.005). Overall seroprevalence among sexually active women gradually increased with age. Women from rural regions had significantly lower overall seroprevalence (Odds Ratio (OR) = 0.7; 95% CI: 0.6-0.9, versus metropolitan regions, P < 0.001). With increasing number of sexual partners, women were at higher risk of seropositivity of any type (OR = 2.6; 95% CI: 1.7-3.9 for > = 4 partners versus 1 partner, P < 0.001). Wives were at higher risk of seropositivity for HPV 16/18/6/11 when reporting having a husband who had an extramarital sexual relationship (OR = 2.0; 95% CI: 1.6-2.5, versus those whose husbands having no such relationship, P < 0.001). There was a strong association between HPV 16 seropositivity and presence of high-grade cervical lesions (OR = 6.5; 95% CI: 3.7-11.4, versus normal cervix, P < 0.001).
HPV seroprevalence differed significantly by age, geography, and sexual behavior within China, which all should be considered when implementing an optimal prophylactic HPV vaccination program in China.
Human papillomavirus; Seroprevalence; China